Diborane (B2H6) is a toxic and pyrophoric gas that is very readily hydrolysed and oxidised. It must be handled with utmost precautions and must be shipped and stored at temperatures below −20° C. In order to reduce the hazards of diborane, complexes of borane (BH3) with donor molecules like ethers, sulfides, amines and phosphines are invariably used for organic reactions, especially for the reduction of functional groups and for hydroboration reactions with alkenes and alkynes. Functional groups reduced by such borane complexes include aldehyde, ketone, lactone, epoxide, ester, amide, oxime, imine and nitrile groups.
The most used source of borane is a tetrahydrofuran (THF) solution of the borane-THF complex, which is commercially available, usually with a concentration of 1 mol/l. However, the borane-THF complex is prone to thermal decomposition by ether cleavage of the tetrahydrofuran ring, leading to butoxyboranes and ultimately to tributylborate as decomposition products. According to U.S. Pat. No. 6,048,985, the storage stability of borane-THF complex in THF solution is increased significantly at low temperatures, even for solutions with higher concentrations.
Borane reagents with other complexing agents are available but suffer from inherent disadvantages. For example, sulfide boranes are highly concentrated but their commercial use is limited because of their strong odor. Numerous borane complexes with aliphatic and aromatic amines are known, but their reactivity is frequently not sufficient to reduce a specific functional group. Moreover, such complexing agents are sometimes difficult to remove from the reaction mixture and isolation of the desired product may become laborious.
Pyridine forms an amine borane that is not moisture sensitive and very useful for reductive aminations and reductions in protic media. Pyridine borane is commercially available and often used in acetic acid to increase the reactivity of the borane. Unfortunately, it is thermally unstable and must be kept at temperatures less than 54° C. to avoid decomposition via hydroboration/polymerization processes. Its shelf-life at ambient temperature is only 6 months, Borane complexes of pyridine, 2-n-propylpyridine, 3-methylpyridine, 3-ethylpyridine and 4-ethylpyridine are liquids which violently decompose upon distillation (Mooney E. F. et al., J. Inorg. Nucl. Chem 1968, 30, p. 1439). 2-Picoline borane (mp. 50° C.), 2-ethylpyridine borane (mp, 50-51° C.), 2,6-lutidine borane (mp. 106-107° C.) and 2,4,6-collidine borane (mp. 99-100° C.) have been isolated as solids.
It is evident that the nature of the complexing agent strongly affects the stability and reactivity of the borane reagent as well as the conditions at which a reaction can be run and the work-up procedure.
Therefore, it is desirable to develop new borane reagents with improved stability and reactivity properties and methods of using them in order to complement the range of available borane reagents and to achieve a better efficiency for organic transformations employing borane reagents.